1-halo-1-nitro disulfides



United States Patent Office 3,429,931 Patented Feb. 25, 1969 3,429,931l-HALO-l-NITRO DISULFIDES Joseph G. E. Fenyes and Gustave K. Kohn,Berkeley,

Calif., assignors to Chevron Research Company, San

Francisco, Calif., a corporation of Delaware No Drawing. Filed Sept. 7,1965, Ser. No. 485,613 US. Cl. 260--608 6 Claims Int. Cl. Aln 149/16;C07c 149/16, 149/30 ABSTRACT OF THE DISCLOSURE Disulfides of the formulaRCSSR wherein X is halogen of atomic number 17 to 35, R is alkyl of 1 tocarbon atoms and R is an organic radical derived from asulfhydryl-containing compound. For instance, R' may be alkyl,cycloalkyl, haloalkyl, aryl, carboxyacyl, carboxyalkyl, carboxyaryl oralkoxycarbonylalkyl. These disulfides are useful as fungicides.

This invention is directed to a new class of organic disulfides andtheir use in biological applications. More particularly, this inventionconcerns a group of organic disulfides which contain thel-halo-1-nitroalkylthio group and their use as fungicides.

The unique class of compounds of this invention may be considered asbeing made up of two portions each derived from separate precursors. Thel-halo-l-nitroalkylthio group which partly characterizes all of thesenew disulfides derives from l-halo-l-nitroalkylsulfenyl halide Theremaining portion of the compounds of the present invention derives froman organic sulfhydryl compound.

In terms of structure, the disulfides of this invention may berepresented by the formula:

is the portion derived from the sulfenyl halide, and -S-R' is thatderived from the sulfhydryl compound. In the above formula, X is halogenof atomic number 17 to 35, i.e., chlorine and bromine, and R is alkyl offrom 1 to 5 carbon atoms.

The l-halo-l-nitroalkylsulfenyl halide precursor of the disulfides ofthis invention may be prepared by reacting the alkali or alkaline earthmetal salt of a primary nitroalkane with sulfur monochloride in thepresence of an inert, anhydrous, nonhydroxylic medium, such as ether, toform a bis-(l-nitroalkyl) disulfide and cleaving the disulfide withhalogen, preferably chlorine. Examples of appropriate sulfenyl halideprecursors are: l-chloro-lnitroethylsulfenyl chloride,1-bromo-l-nitroethylsulfenyl chloride, 1 chloro 1 nitropropyl sulfenylbromide, l-bromo-l-nitrobutylsulfenyl chloride,l-chloro-l-nitrohexylsulfenyl bromide, etc.

The sulfhydryl residue, SR', may originate from a Wide variety oforganic sulfhydryl compounds. Hence R represents a large group oforganic radicals. In accordance with this invention R is an organicradical consisting of from 1 to carbon atoms, from 0 to 10 heteroatomsselected from the group consisting of oxygen, nitrogen, sulfur, andhalogen of atomic number 17 to 35, i.e., chlorine and bromine, andhydrogen. More usually, R will represent an organic radical consistingof from about 1 to 15 carbon atoms, from O to 3 oxygen atoms, 0 to 1halogens of atomic number 17 to and hydrogen. The hydrogen of thesecompounds will satisfy the valences of the carbon atoms not fullysatisfied by other carbon atoms or heteroatoms and the valences of thoseheteroatoms whose valences are not fully satisfied by carbon or otherheteroatoms. Generally, the molecular weight of R will be less thanabout 500 and more generally less than 100. Additionally, it ispreferred that 'R' be free of nucleophilic groups such as sulfhydryl,amino, N-substituted amino, imino, hydroxyl, etc. and free of aliphaticunsaturation, i.e., ethylenic or acetylenic unsaturation. The presenceof such nucleophilic groups may cause degradation of the disulfides viaattack of the halogen groups in them. As used herein the termnucleophilic group defines electron-donating groups which would tend toreact with the halogen of the l-halo-l-nitroalkyl portion of thedisulfides of this invention under normal storage conditions.Preferably, R represents a hydrocarbyl radical free of such nucleophilicgroups and aliphatic unsaturation having from 1 to 25 carbons. Even morepreferred are the compounds where R is alkyl of l to 10 carbons.

The organic sulfhydryl compounds from which SR' is derived includesaturated aliphatic mercaptans, saturated alicyclic mercaptans, aromaticmercaptans such as thiophenols, benzyl mercaptans, naphthyl mercaptans,etc., thiocarboxylic acids, thiodicarboxylic acids, mercapto-substitutedcarboxylic acids, mercapto-substituted esters of carboxylic acids andother similar sulfhydryl-containing compounds. Furthermore, theseorganic sulfhydryl precursors may be singly substituted with inertsubstituents such as chloro, bromo and alkyl groups.

Correspondingly, R may represent alkyl, cycloalkyl, haloalkyl, aryl suchas phenyl, halophenyl, naphthyl, benzyl, halobenzyl, tolyl, etc.,carboxyacyl such as acetyl, propanoyl, butyryl, benzoyl, naphthoyl,etc., carboxyalkyl, carboxyaryl such as carboxyphenyl,carboxyhalophenyl, etc., alkoxycarbonylalkyl, etc.

The following structural formulae illustrates some of the various groupsof disulfides which fall within this invention.

III.

IV. N02

wherein m and n are integers from 1 to 10, preferably from 1 to 4, q isan integer from to 1, R" is selected from the group consisting of loweralkyl, e.g. 1-6 carbon atoms, nitro, carboxyl, chloro and bromo and Rand X are as previously defined.

Illustrative of the disulfides according to this invention are:methyl-l-bromo-l-nitroethyl disulfide, methyl-1- chloro-l-nitroethyldisulfide, methyl-l-chloro-l-nitropropyl disulfide,methyl-l-bromo-1-nitropropyl disulfide, ethyl-l-chloro-1-nitroethyldisulfide, propyl-l-bromo-lnitroethyl disulfide,propyl-l-chloro-l-nitrobutyl disulfide, hexyl-l-chloro-l-nitroethyldisulfide, octyl-l-chloro-lnitrohexyl disulfide,dodecyl-l-bromo-l-nitroethyl disulfide, cyclohexyl-l-chloro-lnitropropyl disulfide, cyclo butyl-l-chloro-l-nitropropyl disulfide,phenyl-l-chlormlnitroethyl disulfide, benzyl-l-chloro-l-nitroethyldisulfide, p-chlorophenyl-l-chloro-l-nitroethyl disulfide,p-chlorophenyl-l-bromo-l-nitrobutyl disulfide,p-bromophenyl-lbromo-l-nitropropyl disulfide,p-tolyl-l-chloro-l-nitroethyl disulfide,p-nitrophenyl-l-chloro-l-nitroethyl disulfide,acetyl-l-chloro-l-nitroethyl disulfide, acetyl-l-bromol-nitrobutyldisulfide, propanoyl-l-chloro-l-nitropropyl disulfide,butyryl-l-chloro-l-nitroethyl disulfide, hexanoyll-bromo-l-nitroethyldisulfide, decanoyl-l-chloro-l-nitropropyl disulfide, octadecanoyl 1chloro-l-nitropropyl disulfide, benzoyl-l-chloro-l-nitroethyl disulfide,benzoyll-bromo-l-nitrohexyl disulfide, toluoyl-l-chloro-l-nitroethyldisulfide, l-chloro-l-nitroethyldithio acetic acid,3-(l-chloro-l-nitroethyldithio) propionic acid, 4-(1-chloro-l-nitropropyldithio) butanoic acid, 4-(1-bromo-lnitrohexyldithio)pentanoic acid, 8-(l-chloro-l-nitroethyldithio) decanoic acid,ethyl-l-chloro-l-nitroethyldithio acetate,methyl-3-(l-bromo-1-nitrobutyldithio) propionate,butyl-8-(l-chloro-l-nitrohexyl) octonoate, etc.

As previously indicated, the novel disulfides of this invention may beprepared by reacting a l-halo-l-nitroalkylsulfenyl halide with anorganic sulfhydryl compound. This displacement reaction may be carriedout neat or in the presence of inert solvents such as benzene, toluene,hexane, heptane, ether, etc. In order to facilitate the rate ofreaction, heat may be applied. For instance, the reaction may beconducted at the reflux temperature of the solvent.

The following examples are presented to illustrate methods by which thenovel disulfides of this invention are prepared. These examples areofiered only by way of illustration and are not limiting on theinvention described herein.

EXAMPLE I A 9.5 gm.-portion of l-chloro-l-nitropropylsulfenyl chloridedissolved in 50 mls. hexane was charged to a flask and cooled to C. Intothis mixture were bubbled 2.4 gm. of methyl mercaptan. The mixture wasallowed to stand for approximately .14 hours after which the hexane wasstripped off. Distillation to C. at 1.0 mm. Hg gave 9.4 gms.ethyl-l-chloro-l-nitropropyl disulfide. This compound was observed as apale yellow oil.

Its analysis was theory, percent Cl, 17.6; S, 31.8. Found: Cl, 18.0; S,30.4.

EXAMPLE II A 3.8 gm.-portion of p-chlorothiophenol dissolved in 50 mls.ether was charged to a vessel. To this mixture were added 4.65 gms.l-chloro-l-nitroethylsulfenyl chloride. The contents were stirred forapproximately 14 hours after which the ether was stripped off. Filteringof the product through celite gave 5.5 gms.p-chlorophenyl-lchloro-l-nitroethyl disulfide.

This compound was observed as a yellow oil having the followinganalysis: Theory, percent CI, 25.0; S, 22.5. Found: Cl, 25.9; S, 21.3.

EXAMPLE HI A 2.5 gm.-portion of thiolacetic acid was placed in a testtube and cooled in an ice bath. To this acid were added dropwise 5.5gms. l-chloro-l-nitroethylsulfenyl chloride while stirring with a woodenstirrer. Evolution of gaseous HCl was observed. The mixture was allowedto stand in an ice bath for one-half hour and then was stripped to 30 C.under a water vacuum. The stripped mixture was further stripped to 50 C.about 0.1 mm. Hg and then fractionally distilled. A 6.3 gm.-portion ofacetyl-l-chloro-l-nitroethyl disulfide was recovered at 73 C., 0.06 mm.Hg to 80 C., 0.1 mm. Hg.

This compound was observed as a colorless oil having the followinganalysis: Theory, percent Cl, 16.5; S, 29.7. Found: Cl, 13.90; S, 30.65.

EXAMPLE IV A 5.3 gm.-portion of 3-mercaptopropionic acid dissolved in'50 ml. of benzene was charged to a vessel. To this mixture was added a9.5 gm.-portion of l-chloro-lnitropropylsulfenyl chloride. After theaddition, the temperature was raised from ambient to 60 C. for 5-7minutes. The benzene was evaporated and the product was then stripped to74 C. about 0.2 mm. Hg. A 12 gm.- portion of3-(l-chloro-l-nitropropyldithio) propionic acid was recovered as a dark,very viscous liquid.

Its analysis was: Theory, percent Cl, 13.65; S, 24.7. Found: Cl, 13.93;S, 24.42.

EXAMPLE V A 5.3 gm.-portion of l-chloro-l-nitroethylsulfenyl chloridedissolved in 20 ml. benzene was charged to a vessel. To this mixture wasadded dropwise an 8.8 gm.- portion of methyl thioglycolate in 30 ml.benzene. The contents were boiled gently for 20-30 minutes while beingstirred. The benzene was then evaporated at subatmospheric pressure andthe product was stripped to 68 C. about 0.2 mm. Hg. An 11.5 gun-portionof methyll-chloro-l-nitroethyldithio acetate was recovered as a darkorange liquid.

Its analysis was: Theory, percent Cl, 14.43; S, 26.10. Found: Cl, 14.28;S, 25.72.

EXAMPLE VI A 9.5 gm.-portion of l-chloro 1 -nitropropylsulfenyl chloridedissolved in benzene was charged to a vessel. To this mixture was addeda 6.2 gm.-portion of benzyl mercaptan dissolved in benzene. The additiontook approximately 30 minutes. The mixture was stirred and heated to agentle reflux for a 30 minute period after which the benzene wasstripped off at subatmospheric pressure. Further stripping yielded 14.7gm. of benzyl-l-chloro-l-nitropropyl disulfide. Its analysis was: Theorypercent Cl, 12.76; S, 23.08. Found: C1, 11.90; S, 23.1.

The analyses of other analogously prepared disulfides of this inventionare contained in Table I.

TABLE I Analysis Compound Element Theory Foundl-chloro-l-nitropropyldlthio acetic acid Cl 14. 43 14. 26. 09 26.l-chloro'l-nttroethyldithio acetic acid l5. 3 16. 60 27. 63 27. 35 3-(l-chloro-l-nitroethyldithio)propionic acid 14. 4 15. 72 S 26. 1 25. 80Ethyl1-ch1oro-l-nitroethy1 disulfide 17. 67 20. 48 8 31. 78 30. 65l-ehloro-1-nitroethyl-p-bromopheny1 disulfide 24. 31 24. 50

1-chloro-l-nitropropyl-p-bromopheny1 disulfide B 23. 32 23. 55

l-ehloro-1-nitroethyl-p-chlorobenzyl disulfide C g6S-(l-ehloro-l-nitroethylthio)ethyl xanthate 2; 5%: 2g

. l S-(l-chloro-l-nitropropylthio)-ethyl xanthate 12. 85 12. 73 S 34. 8735. 35 1-chloro-1nltropropyl-p-ehlorobenzyl disulfide Z41 2-methoxyethyl1-chloro-l-nitroethy1dithioacetate g1 2'methoxyethyll-ehloro-l-nitro-propyldithioacetate- 55gLchloro-l-nitropropyldithiornethyl acetate 13: 65 88 S 24. 69 24. 222-(l-chloro-l-nitroethyldithlo)propionic acid 14. 37 14. 38 25. 99 25.63 2-(l-chloro-l-nitropropyldithio)propionic acid 2g g3oCarhoxyphenyl-l-chloro-l-nitropropyl disulfide Ol 11: 52 11:18 20. 8320. 41-

The novel disulfides of this invention are useful as fungicides. Anumber of the compounds of this invention were tested for fungicidalactivity by means of the mycelial drop test. This test is designed tomeasure the fungitoxic activity of fungicidal amounts of each chemicalin terms of their degree of inhibition upon mycelial growth. Eachfungitoxic compound to be tested was dissolved in acetone in dilutionsas indicated in Table II. Paper discs previously inoculated byimpregnation with equal amounts of particular fungus mycelium and placedon potato dextrose agar medium were treated by applying a precise andequal volume of each of these fungicidal solutions to their center.Following treatment with the fungitoxic amount of the chemical, thediscs were incubated along with inoculated but untreated control discsat ambient temperatures until such time that these untreated controldiscs were filled with mycelial growth. Activity of the fungitoxicchemical tested was determined by comparative measurements of radii ofmycelial growth away from the edge of the disc in treated and untreatedsamples. From this comparison a percent inhibition of growth area isdetermined. The results of this test for various fungitoxic chemicals onthe particular fungus mycelium are indicated in Table II.

Aside from the specific formulation and application of the class ofcompounds of the invention as represented by the foregoing tests, thesecompounds may be dispersed in or upon other inert liquid and solidcarriers, such as inert clay, xylenes, etc. The solid carriers may be inthe form of a dust, or used in conjunction with a suitable wetting agentto form a wettable powder. The fungitoxic compounds of the invention mayalso be formulated with other solvents, dispersing agents, oremulsifying agents. FUIlIhCL'thCSS compounds may not only be appliedalone or in mixtures with other compounds of the disclosed class, butmay also be used in combination with other active toxicants in theformulation of fungicidal compo sitions.

The compounds may be applied to any environmental area which is a hostto fungus or susceptible to fungus attack. For example, the fungicidalcompositions may be sprayed or otherwise applied directly to a plant orother host, may be applied to the plant seed, sprayed upon the soil orother plant environment, or used in similar ways so as to effect thecontrol of fungus and fungusdiseases.

As will be evident to those skilled in the art, various modifications onthis invention can be made or followed,

TABLE II Concen- Fungus Mycelz'u'm, percent Inhibition Compound tration,

p.p.m. Pythium Fusarium Rhizoctonia VerticilliumMethyl-lmhloro-1-nitroethyl disulfide 500 100 98 98p-Chlorophenyl-l-chioro-l nitroethyl dlsulfide- 500Acetyl-l-chloro-1-nltro-ethyl disulfide 500l-chloro-l-uitroethyldithio-aeetlc acid 5003-(l-chloro-l-nltropropyldlthio) propionic acid- 500l-chloro-l-nitropropy dlthlo-acetie acid 600 in the light of theforegoing disclosure and discussion, without departing from the spiritor scope of the disclosure or from the scope of the following claims.

What is claimed is:

1. Disulfide of the formula R- -SSR wherein X is halogen of atomicnumber 17 to 35, R is alkyl of 1 to 5 carbon atoms and R is ahydrocarbyl radical of about 1 to 15 carbon atoms which is free ofaliphatic unsaturation or phenyl singly substituted with nitro, chloroor bromo or benzyl singly substituted with nitro, chloro or bromo.

2. Disulfide of the formula N 02 R?SSR' wherein X is halogen of atomicnumber 17 to 35, R is alkyl of 1 to 5 carbon atoms and R is ahydrocarbyl radical of about 1 to 15 carbon atoms which is free ofaliphatic unsaturation.

3. An organic disulfide of the formula N 0 references cited.

CHARLES B. PARKER, Primary Examiner. D. R. PHILLIPS, Assistant Examiner.

US. Cl. X.R.

